Genetic Variant GALNT8:p.Asn532Ser (chr12-4765380-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017417.2(GALNT8):c.1595A>G(p.Asn532Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000119 in 838,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N532T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

GALNT8
NM_017417.2 missense, splice_region

Scores

Splicing: ADA: 0.0005637

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Publications

0 publications found

Variant links:

Genes affected

GALNT8 (HGNC:4130): (polypeptide N-acetylgalactosaminyltransferase 8) This gene encodes a member of the UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. GalNAc-Ts initiate mucin-type O-linked glycosylation in the Golgi apparatus by catalyzing the transfer of GalNAc to serine and threonine residues on target proteins. They are characterized by an N-terminal transmembrane domain, a stem region, a lumenal catalytic domain containing a GT1 motif and Gal/GalNAc transferase motif, and a C-terminal ricin/lectin-like domain. GalNAc-Ts have different, but overlapping, substrate specificities and patterns of expression. [provided by RefSeq, Jul 2008]

GALNT8 links:

ENSG00000255639 (HGNC:):

ENSG00000255639 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13363844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT8	NM_017417.2 link	c.1595A>G	p.Asn532Ser	missense_variant, splice_region_variant	Exon 10 of 11	ENST00000252318.7	NP_059113.1	Q9NY28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT8	ENST00000252318.7 link	c.1595A>G	p.Asn532Ser	missense_variant, splice_region_variant	Exon 10 of 11	1	NM_017417.2	ENSP00000252318.2		Q9NY28
ENSG00000255639	ENST00000648836.1 link	c.1385A>G	p.Asn462Ser	missense_variant, splice_region_variant	Exon 14 of 15			ENSP00000497305.1		A0A3B3ISG8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000119

AC:

AN:

838716

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

427328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18888

American (AMR)

AF:

0.00

AC:

AN:

23392

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16562

East Asian (EAS)

AF:

0.00

AC:

AN:

30950

South Asian (SAS)

AF:

0.00

AC:

AN:

57234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2602

European-Non Finnish (NFE)

AF:

0.00000165

AC:

AN:

605792

Other (OTH)

AF:

0.00

AC:

AN:

37362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.0043

.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

PhyloP100

1.5

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.1

.;N

REVEL

Benign

0.090

Sift

Benign

0.39

.;T

Sift4G

Benign

0.41

.;T

Polyphen

0.38

.;B

Vest4

0.12

MutPred

0.53

.;Loss of sheet (P = 0.0315);

MVP

0.12

MPC

0.084

ClinPred

0.33

GERP RS

2.8

Varity_R

0.085

gMVP

0.22

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00056

dbscSNV1_RF

Benign

0.0060

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over